The transformation of the mouse cell line NIH 3T3 has been induced following transfection with DNAs from various human and animal tumors. In all instances studied to date, the genes responsible for transformation have been the cellular homologs of retrovirus onc genes. Questions remain concerning this process: (1) what roles do the genes responsible for transformation in the transfection assay play in tumor development in vivo; and (2) how is the activation of c-onc genes to produce transformation achieved? Our approach to these questions uses as a model system, the human neuroblastoma, a cancer in which the number of gene changes responsible for tumorigenesis is believed to be small and from which we have established multiple cell lines with stable, defined karyotypes. Our analysis will compare the transforming sequences from different neuroblastomas and, through in situ hybridization, will assign the individual transforming sequences to specific sites in the neuroblastoma karyotype. The hybridization of onc gene sequence probes to neuroblastoma metaphases will determine whether activation of c-onc genes is associated with particular chromosome rearrangements or with the novel chromosome abnormalities, homogeneously staining regions and double minutes. We also will use monoclonal antibodies and cell surface glycoprotein analysis to study the surface membrane alterations produced by transformation in this system.